Research projects initiated during the past four years will be continued, with primary attention to the mechanism of action of thyroid hormone. We will study the increase in RNA polymerase induced by thyroid hormone in liver cell nuclei, and then attempt to identify whether this is due to alteration of the protein or induction of new protein synthesis. The presence of cytoplasmic factors able to induce synthesis of new polymerase, or phosphorylation of polymerase protein will be investigated. Antibodies will be prepared to polymerase and used to quantitate the protein molecule and to identify the amount of protein present in various types of liver nuclei. The reduction in T3 nuclear receptors present in immature animals, hepatectomized animals, starved animals, or tumor bearing animals will be investigated. We will determine whether chromatin and nuclei from such animals have altered ability to bind thyroid hormone nuclear receptors. Phosphokinase activity in nuclei will be determined in animals with various states of thyroid function, and types of kinase will be studied and separated by column chromatography. Induction of specific phosphokinases by thyroid hormone action will be investigated.